Systemic delivery of HER2-retargeted oncolytic-HSV by mesenchymal stromal cells protects from lung and brain metastases

Valerio Leoni, Valentina Gatta, Arianna Palladini, Giordano Nicoletti, Dario Ranieri, Massimiliano Dall'Ora, Valentina Grosso, Martina Rossi, Francesco Alviano, Laura Bonsi, Patrizia Nanni, Pier Luigi Lollini, Gabriella Campadelli-Fiume

Research output: Contribution to journalArticlepeer-review

Abstract

Fully retargeted oncolytic herpes simplex viruses (o-HSVs) gain cancer-specificity from redirection of tropism to cancer-specific receptors, and are non-attenuated. To overcome the hurdles of systemic delivery, and enable oncolytic viruses (o-viruses) to reach metastatic sites, carrier cells are being exploited. Mesenchymal stromal cells (MSCs) were never tested as carriers of retargeted o-viruses, given their scarse-null expression of the cancer-specific receptors. We report that MSCs from different sources can be forcedly infected with a HER2-retargeted oncolytic HSV. Progeny virus spread from MSCs to cancer cells in vitro and in vivo. We evaluated the organ distribution and therapeutic efficacy in two murine models of metastatic cancers, following a single i.v. injection of infected MSCs. As expected, the highest concentration of carrier-cells and of viral genomes was in the lungs. Viral genomes persisted throughout the body for at least two days. The growth of ovarian cancer lung metastases in nude mice was strongly inhibited, and the majority of treated mice appeared metastasis-free. The treatment significantly inhibited also breast cancer metastases to the brain in NSG mice, and reduced by more than one-half the metastatic burden in the brain.

Original languageEnglish
Pages (from-to)34774-34787
Number of pages14
JournalOncotarget
Volume6
Issue number33
DOIs
Publication statusPublished - 2015

Keywords

  • Mesenchymal stem cells
  • Metastases
  • Oncolytic herpes simplex virus
  • Systemic delivery
  • Viral retargeting

ASJC Scopus subject areas

  • Oncology

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